Tailored Anti-miR Decorated Covalent Organic Framework Enables Electrochemical Detection of Salivary miRNAs for Mild
Pranay Saha1, David Skrodzki2, Teresa Aditya1
1Department of Nuclear Engineering, The Pennsylvania State University, University Park, PA, 16802, USA.
Abstract:
MicroRNAs (miRNAs) play pivotal role as biomarkers for various diseases, with salivary miRNAs offering a non-invasive diagnostic tool. For mild traumatic brain injury (mTBI), salivary miRNAs like miR-let7a, miR-21, and miR-30e show promise for early detection of subtle injuries lacking reliable indicators. To advance the detection of mTBI-related salivary miRNAs, this study integrates anti-miRNA and miRNA hybridization-based sensing with the development of a nanoscale covalent-organic framework (COF) platform. COFs, with their highly customizable structures, large surface area, and biocompatibility, serve as a versatile foundation for biosensing applications. Here, post-synthetic modification (PSM) of COFs is introduced for essential covalent conjugation of streptavidin for further immobilization of methylene blue-labeled and biotinylated Anti-miRNAs. Furthermore, the layer-by-layer assembly of conductive polymers enhanced the biosensor's electrical performance, enabling ultrasensitive and multiplexed detection of salivary miRNAs. Validated with samples from mixed martial arts participants and confirmed by polymerase chain reaction (PCR), this COF-based platform demonstrates robust accuracy and reliability. By combining COF functionalization with advanced electrode design, it offers a powerful, non-invasive solution for early mTBI detection and broader biomedical applications.
Insights
This study introduces a novel biosensor using nanoscale covalent-organic frameworks (COFs) for non-invasive detection of salivary microRNAs (miRNAs) linked to mild traumatic brain injury (mTBI). The advanced platform offers accurate and reliable early diagnosis of mTBI.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Molecular Diagnostics
Background:
- MicroRNAs (miRNAs) are crucial biomarkers for disease detection, with salivary miRNAs offering a non-invasive diagnostic approach.
- Mild traumatic brain injury (mTBI) diagnosis is challenging due to subtle injuries lacking reliable early indicators.
- Existing diagnostic methods for mTBI often lack the sensitivity and non-invasiveness required for early detection.
Purpose of the Study:
- To develop an ultrasensitive and multiplexed biosensor for detecting specific salivary miRNAs associated with mTBI.
- To leverage nanoscale covalent-organic frameworks (COFs) for enhanced biosensing capabilities.
- To create a reliable, non-invasive tool for early mTBI detection.
Main Methods:
- Integration of anti-miRNA and miRNA hybridization-based sensing with a nanoscale COF platform.
- Post-synthetic modification (PSM) of COFs for streptavidin conjugation and immobilization of labeled anti-miRNAs.
- Layer-by-layer assembly of conductive polymers to improve biosensor electrical performance.
Main Results:
- The COF-based platform enabled ultrasensitive and multiplexed detection of salivary miRNAs.
- The biosensor demonstrated robust accuracy and reliability when validated with samples from mixed martial arts participants.
- Results were confirmed using polymerase chain reaction (PCR).
Conclusions:
- The developed COF-based biosensor provides a powerful and non-invasive solution for early mTBI detection.
- The platform's design combines COF functionalization with advanced electrode engineering for superior performance.
- This technology holds potential for broader biomedical applications beyond mTBI diagnosis.
